Netherlands Cancer Institute

Labcorp Plasma Detect is the first clinically validated, whole-genome sequencing MRD solution for early-stage colon cancer BURLINGTON, N.C., April 5, 2024 /PRNewswire/ -- Labcorp (NYSE: LH), a global leader of innovative and comprehensive laboratory services, announced today the launch of Labcorp® Plasma Detect™, the first clinically validated, tumor-informed, whole-genome sequencing circulating tumor DNA (ctDNA) molecular residual disease (MRD) solution in early stage colon cancer to identify patients at increased risk of recurrence after surgery or adjuvant chemotherapy (ACT). This solution, which is designed for research use but also suitable for clinical applications, can be applied across solid tumors with a scalable and standardized approach to facilitate faster turnaround times while maintaining high analytical performance. The launch of the Labcorp Plasma Detect MRD solution further enhances Labcorp's leadership in precision oncology across the solid tumor oncology care continuum. Labcorp Plasma Detect builds on the successful deployment of two existing liquid biopsy platforms – Labcorp® Plasma Focus™, a targeted approach, and Labcorp® Plasma Complete™, a comprehensive profiling solution, both with utility for clinical research and clinical applications. All three solutions were developed by Personal Genome Diagnostics, Inc. (PGDx®), a Labcorp company, and are performed in the PGDx Baltimore CAP-accredited and CLIA-certified laboratory. "Labcorp Plasma Detect is a significant achievement, enhancing Labcorp's liquid biopsy portfolio and strengthening our position at the forefront of driving better patient outcomes in oncology," said Shakti Ramkissoon, M.D., Ph.D., vice president, medical lead for oncology at Labcorp. "Labcorp Plasma Detect delivers a high-impact solution for clinical research and biopharmaceutical drug development to support retrospective and prospective clinical trials with the goal of improving patient outcomes in early stage disease." The Labcorp Plasma Detect integrated whole-genome sequencing sample-to-report workflow was developed under PGDx's quality management system and design control process, undergoing rigorous analytical and clinical validation to demonstrate high sensitivity and specificity for ctDNA detection. It is backed by Labcorp's global network and expertise and does not require the manufacturing of patient-specific, bespoke panels, making it feasible to implement for research programs and clinical trials globally. Labcorp Plasma Detect is currently clinically validated for early-stage colon cancer, with ongoing efforts to expand into other indications, including lung cancer and bladder cancer. In collaboration with the Netherlands Cancer Institute (NKI), Labcorp Plasma Detect validation data will be presented during a podium presentation – Clinical validity of post-surgery circulating tumor DNA testing in stage III colon cancer patients treated with adjuvant chemotherapy: the PROVENC3 study – at the annual meeting of the American Association for Cancer Research® (AACR®). Labcorp Plasma Detect will also be used to support the MEDOCC-CrEATE trial, an interventional, randomized study that will provide insight into the willingness of stage II colon cancer patients to be treated with ACT and whether ACT can prevent recurrences in a high-risk population.1 "There is an unmet clinical need to better determine who benefits from adjuvant treatment after surgical resection. The tumor-informed whole genome sequencing-based approach of Labcorp Plasma Detect tracks thousands of tumor-specific mutations in cell-free DNA, thereby offering a highly sensitive and specific ctDNA MRD test," said Remond Fijneman, associate group leader and principal investigator at NKI. "Combined with the relatively short turnaround time, which meets the timelines for clinical decision-making, ctDNA-guided treatment de-escalation is now within reach." To learn about Labcorp Plasma Detect, visit About Labcorp Labcorp (NYSE: LH) is a global leader of innovative and comprehensive laboratory services that helps doctors, hospitals, pharmaceutical companies, researchers and patients make clear and confident decisions. We provide insights and advance science to improve health and improve lives through our unparalleled diagnostics and drug development laboratory capabilities. The company's more than 67,000 employees serve clients in approximately 100 countries, provided support for 84% of the new drugs and therapeutic products approved in 2023 by the FDA, and performed more than 600 million tests for patients around the world. Learn more about us at . __________________________________ 1 Circulating tumor DNA guided adjuvant chemotherapy in stage II colon cancer (MEDOCC-CrEATE): study protocol for a trial within a cohort study SOURCE Labcorp

­-- AB248 demonstrates over 500-fold preference for CD8+ T cells compared to other cell types; selectivity intended to optimize efficacy and mitigate toxicities observed with broadly acting IL-2 therapies – -- In variety of preclinical models, AB248 demonstrates improved anti-tumor activity and reduced toxicity compared to untargeted “not-α”IL-2, as well as the ability to reinvigorate dysfunctional T cells -- -- Preclinical data support evaluation of AB248 as monotherapy and in combination with an anti-PD-1 inhibitor in an ongoing Phase 1a/1b clinical trial in locally advanced or metastatic solid tumors -- SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)-- Asher Biotherapeutics, a biotechnology company developing precisely-targeted immunotherapies for cancer, autoimmune, and infectious diseases, today announced the publication of two manuscripts in Cancer Discovery, a journal of the American Association for Cancer Research, detailing the design of AB248 and reviewing preclinical data supporting its development as a potentially best-in-class interleukin-2 (IL-2) therapy. The papers were authored by Asher Bio scientists and collaborators at The Netherlands Cancer Institute (NKI), respectively, and published online in Cancer Discovery on April 2, 2024. “We are delighted to announce the publication of preclinical data on AB248, our lead product candidate for the treatment of solid tumors, in a prestigious cancer research and medicine journal”, said Andy Yeung, Chief Technology Officer of Asher Bio. “These co-published manuscripts are the culmination of several years of great collaboration between Asher Bio scientists and our academic co-founders, Dr. Ton Schumacher, of NKI, and Dr. Robert Schreiber, of Washington University School of Medicine, alongside our collaborator, Dr. Daniela Thommen, of NKI.” “With AB248, we set out to solve a major limitation of existing immune-based medicines – namely, the significant off-target effects that come from acting on multiple cell types simultaneously”, commented Ivana Djuretic, Chief Scientific Officer of Asher Bio. “AB248 was designed to potently and selectively activate CD8+ T cells, which are responsible for driving anti-tumor activity, while avoiding NK cells and Tregs, which can act as a pharmacological sink, contribute to toxicities, and suppress the immune system more broadly. Preclinical data from the Asher Bio, Schreiber and Thommen labs together reinforce the power of AB248’s highly differentiated profile, showing an unprecedented level of selectivity for CD8+ T cells, as well as enhanced anti-tumor activity and improved tolerability, and further support the evaluation of AB248 in our ongoing Phase 1a/1b trial.” Preclinical Data Suggest AB248 Offers Improved Therapeutic Index and CD8+ T Cell Selectivity In the first publication entitled, “CD8+ T cell-targeted IL-2 promotes robust effector T cell responses to mediate potent anti-tumor immunity,” lead author Dr. Kelly Moynihan, Ph.D., Senior Director and Project Team Leader at Asher Bio, described the rationale for, and the design of, AB248, and reviewed nonclinical data suggesting AB248 offers an improved therapeutic index compared to broadly acting IL-2-based therapies. While high dose IL-2 therapy is approved for the treatment of certain cancers, its clinical use is limited due to life-threatening toxicities. A next generation of IL-2 therapies, “not-α” IL-2s, were subsequently introduced to mitigate some of the liabilities associated with high dose IL-2 through binding the IL-2 α receptor, such as potent regulatory T cell (Treg) stimulation and vascular leak syndrome (VLS). To-date, however, these “not-α” IL-2 have not demonstrated a meaningful improvement in clinical efficacy and, while VLS appears mitigated, significant toxicities still occur. In preclinical studies, natural killer (NK) cells were responsible for toxicities following treatment with a not-α IL-2 therapy but did not contribute to anti-tumor activity. Asher Bio hypothesized that the therapeutic index of an IL-2 therapy could be improved by selectively targeting CD8+ T cells – which are critical effectors of antitumor immunity – while avoiding other cell types, such as non-specific, innate NK cells and immunosuppressive Treg cells. Asher Bio systematically evaluated the properties needed for effective cis-targeting to CD8+ T cells and generated AB248, a CD8+ T cell selective IL-2. AB248 recapitulates key features of IL-2 biology, including induction of proliferation and enhancement of effector function, but does so selectively in CD8+ T cells across a wide range of concentrations in vitro and in vivo, with over 500-fold preference for CD8+ T cells compared to other cell types. Preclinical data demonstrate the potential of a CD8+ T cell selective IL-2 to improve the therapeutic index of IL-2 and support the advancement of AB248 into the clinic: - In preclinical mouse models, a single dose of AB248’s murine surrogate (CD8-mIL2) demonstrated strongly improved anti-tumor activity and reduced toxicity compared to untargeted not-α IL-2 variants. - Further, CD8-mIL2 drastically increased the number and function of tumor antigen specific T cells and induced a “better effector” population, with a signature consistent with high polyfunctionality and low exhaustion. - Activity depended both on tumor-resident as well as newly infiltrating T cells on therapy. - In non-human primates, treatment with AB248 induced potent and selective CD8+ T cell expansion. Treatment was generally well tolerated despite expansion of CD8+ T cells by 20-fold or more. In summary, AB248 achieved substantial improvements in IL-2’s therapeutic index by selectively targeting all CD8+ T cells without the need to restrict signaling to the tumor site or a single CD8+ T cell subset. Preclinical Data Support Evaluation of AB248 in Combination with Anti-PD-1 Therapy In a paper entitled, “CD8-targeted IL-2 unleashes tumor-specific immunity in human cancer tissue by reviving the dysfunctional T cell pool,” lead author Paulien Kaptein, Division of Molecular Oncology and Immunology at the NKI, reported new preclinical data supporting the evaluation of AB248 in combination with an immune checkpoint inhibitor in models utilizing ex vivo human tumor tissues from patients. T cell-based immunotherapies are a groundbreaking approach to treating some cancers. However, a considerable portion of tumors characterized by T cell infiltration remain unresponsive to immune checkpoint blockade (ICB), suggesting a need for novel strategies to restore effector activity in tumor specific T cells. IL-2-based therapies have been identified as a promising strategy for enhancing T cell responses in ICB-resistant tumors. To evaluate this hypothesis, Asher Bio’s collaborators at the NKI performed a comprehensive analysis of T cell reinvigoration following treatment with AB248. Data show: - Treatment with AB248 broadly armed human intratumoral CD8+ T cells with enhanced effector capacity, specifically enabling reinvigoration of the dysfunctional T cell pool to elicit potent immune activity. - Tumor-specific T cells underwent broader and qualitatively superior activation with AB248 treatment compared to programmed death-1 (PD-1) blockade. - AB248 generated an immunological response in tumors that did not show an immunological response to anti-PD-1, suggesting the presence of a tumor-reactive T cell pool targetable by AB248 that is not responsive to PD-1 blockade alone. - Treatment with AB248 in combination with anti-PD-1 resulted in greater ex vivo responses, supporting the combination of AB248 and anti-PD-1 clinically. “While immune checkpoint inhibitors are an incredibly powerful tool for treating certain cancers, many tumors don’t respond, underscoring the need for new agents that can reinvigorate exhausted T cells and make them susceptible to PD-1 blockade,” said Daniela Thommen, M.D., Ph.D., Group Leader, Department of Molecular Oncology and Immunology at the Netherlands Cancer Institute and senior author on the NKI publication. “New preclinical data published today suggest that treatment with AB248 may stimulate T cells within tumors otherwise resistant to PD-1 therapy, offering a combination strategy that may extend the reach of immuno-oncology regimens across a range of solid tumors. I look forward to initial clinical data from Asher Bio’s ongoing Phase 1a/1b clinical trial, which includes a cohort evaluating AB248 in combination with an anti-PD-1 therapy.” Both publications are now available online through Cancer Discovery: . About AB248 AB248 is a novel CD8+ T cell selective IL-2, generated by fusing a reduced potency IL-2 mutein to an anti-CD8β antibody. It was specifically engineered to selectively and potently activate CD8+ T-cells, while avoiding natural killer (NK) cells, which can act as a pharmacological sink and contribute to toxicity, and regulatory T (Treg) cells, which are immunosuppressive. In preclinical studies, AB248 exhibited an approximately 1,000-fold preference for the activation of CD8+ T cells over NK cells and Tregs. In preclinical murine tumor studies, AB248 demonstrated potent anti-tumor activity both alone and in combination with PD-1 checkpoint blockade in a wide variety of murine tumor models. Asher Bio is currently evaluating AB248 in a Phase 1a/1b clinical trial, AB248-101. The trial consists of a dose escalation and expansion phase to investigate the safety, pharmacokinetics (PK), pharmacodynamics (PD), and anti-tumor activity of AB248 alone and in combination with pembrolizumab in subjects with locally advanced/metastatic solid tumors who failed prior therapies. Please refer to (NCT05653882) for additional details related to this Phase 1a/1b clinical trial. About Asher Bio Asher Bio is a biotechnology company developing therapies to precisely engage specific immune cells to fight cancer, chronic viral infection and autoimmune disease. We utilize our proprietary cis-targeting platform to develop therapies engineered to overcome limitations of other immune-based treatments by selectively activating specific immune cell types with validated disease fighting functionality. Our candidates feature an antibody connected to a modified immunomodulatory protein, such as a cytokine. Our candidate design is intended to enable our candidates to selectively activate the desired immune cells and not other cells that contribute to toxicity or immune suppression. Our lead program AB248, an IL-2 molecule specifically targeted to CD8+ effector T cells, is currently in Phase 1 trials for oncology. Our broader portfolio includes AB821, an IND-ready CD8-targeted IL-21 immunotherapy, and early-stage programs targeting CAR-T cells, myeloid cells and CD4+ T cells. Asher Bio was founded by Ivana Djuretic and Andy Yeung with support from Third Rock Ventures and is located in South San Francisco. For more information, please visit and follow us on X (formerly Twitter) @AsherBio and on LinkedIn.

LB-100 IS SYNERGISTIC WITH WEE1 INHIBITION IN KILLING CANCER CELLS; FINDING OPENS NEW TREATMENT STRATEGY IN ADDITION TO THREE CURRENT LIXTE CLINICAL TRIALS PASADENA, CA, March 27, 2024 (GLOBE NEWSWIRE) -- LIXTE Biotechnology Holdings, Inc. (“LIXTE” or the “Company”) (Nasdaq: LIXT and LIXTW), a clinical stage pharmaceutical company, announced today publication of pre-clinical data in the online journal, Cancer Discovery, showing that its lead clinical compound, LB-100, can force cancer cells to give up their cancer-causing properties in a paper entitled “Paradoxical activation of oncogenic signaling as a cancer treatment strategy.” The finding opens a potentially new treatment strategy in addition to LIXTE’s current three clinical trials. As will be published in the July 2024 issue and posted online today, LB-100 was shown to trigger hyper-activation of the signals that are responsible for the deregulated proliferation of cancer cells, which is the opposite of most of the current generation of cancer therapies. The deliberate hyper-activation of cancer signals becomes lethal when combined with an inhibitor of the WEE1 kinase. This well-tolerated combination proved to be highly effective in killing colon cancer cells in animal models of cancer and in cell culture. Resistance to therapy is the leading cause of death due to cancer. Resistance to LB-100 therapy, however, has been shown to be associated with cancer cells becoming less malignant. Specifically, colon cancer cells that developed resistance to LB-100 had lost many of the features that make the cells cancerous in the first place and were unable to form tumors in experimental animal models. This “tumor suppressive drug resistance” stems from the unique features of LB-100. Although cancer-causing signals force cancer cells to become more cancerous, the hyper-activation of these signals by LB-100 forces cancer cells to suppress these signals and thus become less cancerous. The team of scientists reporting these findings was headed by Professor René Bernards at the Netherlands Cancer Institute and Oncode Institute, Amsterdam. Professor Bernards is a a leader in the field of molecular carcinogenesis and is a member of the Board of Directors of LIXTE. Bas van der Baan, Chief Executive Officer of LIXTE, said, “The effect of LB-100 on cancer cells is unique in that the only way for cancer cells to escape death is to evolve toward a less cancerous behavior. We look forward to testing this concept clinically, which is distinct from the well-characterized enhancement of checkpoint immunotherapy and chemotherapy by LB-100 currently being tested in three clinical trials.” About LIXTE Biotechnology Holdings, Inc. LIXTE Biotechnology Holdings, Inc. is a clinical-stage pharmaceutical company focused on new targets for cancer drug development and developing and commercializing cancer therapies. LIXTE has demonstrated that its first-in-class lead clinical PP2A inhibitor, LB-100, is well-tolerated in cancer patients at doses associated with anti-cancer activity. Based on extensive published preclinical data (see www.lixte.com), LB-100 has the potential to significantly improve outcomes for patients undergoing various chemotherapies or immunotherapies. LIXTE's new approach has no known competitors and is covered by a comprehensive patent portfolio. Proof-of-concept clinical trials are in progress. Forward-Looking Statement Disclaimer This announcement contains certain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, and Section 21E of the Securities Exchange Act of 1934. For example, statements regarding the Company's financial position, business strategy and other plans and objectives for future operations, and assumptions and predictions about future activities, including the continuing development of proprietary compounds, the planning, funding, coordination and potential results of clinical trials, the patent and legal costs to protect and maintain the Company's intellectual property worldwide, and the Company’s ability to obtain and maintain compliance with Nasdaq’s continued listing requirements, are all forward-looking statements. These statements are generally accompanied by words such as "intend," anticipate," "believe," "estimate," "potential(ly)," "continue," "forecast," "predict," "plan," "may," "will," "could," "would," "should," "expect" or the negative of such terms or other comparable terminology. The Company believes that the assumptions and expectations reflected in such forward-looking statements are reasonable, based on information available to it on the date hereof, but the Company cannot provide assurances that these assumptions and expectations will prove to have been correct or that the Company will take any action that the Company may presently be planning. However, these forward-looking statements are inherently subject to known and unknown risks and uncertainties. Actual results or experience may differ materially from those expected or anticipated in the forward-looking statements. Factors that could cause or contribute to such differences include, but are not limited to, regulatory policies, available cash resources, research results, competition from other similar businesses, and market and general economic factors. Readers are urged to read the risk factors set forth in the Company’s filings with the United States Securities and Exchange Commission at https://www.sec.gov. The Company disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise. For more information about LIXTE, Contact: info@lixte.com General Phone: (631) 830-7092; Investor Phone: (888) 289-5533 or PondelWilkinson Inc. Investor Relations pwinvestor@pondel.comRoger Pondel: (310) 279-5965; Laurie Berman: (310) 279-5962